The aim of the proposed research is to analyze and compare the mechanisms by which sodium cyanate and TPCK (L-1-tosylamido-2-phenylethyl ketone) selectively inhibit amino acid incorporation into the proteins of tumor cells. Particular attention will be paid to the inhibition of protein synthesis in colonic adenocarcinoma cells, both in vivo and in vitro. Test systems include tumors induced in rodents by the administration of 1,2-dimethylhydrazine, and transplantable colonic tumors differing in growth properties and metastatic potential. The inhibitory effect of cyanate on protein synthesis in cell lines derived from colonic tumors and maintained in culture requires an activation of the cyanate by the mixed function oxidases. Identification of the reaction products formed in the cytochrome P450-dependent activation step is a major priority in this program.